Summary of Study ST002229

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001419. The data can be accessed directly via it's Project DOI: 10.21228/M89D8V This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002229
Study TitleEstrogen receptor α deficiency in cardiac myocytes reprograms heart-derived extracellular vesicle proteome and induces obesity in female mice (Part 1)
Study SummaryDysregulation of ERα has been linked with increased metabolic and cardiovascular disease risk. Uncovering the impact of ERα deficiency in specific tissues has implications for understanding the role of ERα in normal physiology and disease, the increased disease risk in postmenopausal women, and the design of tissue-specific ERα-based therapies for a range of pathologies including cardiac disease and cancer. Cardiac myocyte-specific ER knockout mice (ERαHKO) were generated to assess the role of ERα in the heart. Female ERαHKO mice displayed a modest cardiac phenotype, but unexpectedly, the most striking phenotype was obesity in female ERαHKO but not male ERαHKO mice. In female ERαHKO mice we identified cardiac dysfunction, mild glucose and insulin intolerance, and reduced ERα gene expression in skeletal muscle and white adipose tissue (WAT). Gene expression, protein, lipidomic and metabolomic analyses showed evidence of contractile and/or metabolic dysregulation in heart, skeletal muscle and WAT. We also show that extracellular vesicles (EVs) collected from the perfusate of isolated hearts from female ERαHKO mice have a distinct proteome, and these EVs have the capacity to reprogram the proteome of a skeletal muscle cell including proteins linked with ERα, fatty acid regulation, lipid metabolism and mitochondrial function. This study uncovers a cardiac-initiated and sex-specific cardiometabolic phenotype that is regulated by ERα.
Institute
Baker Heart and Diabetes Institute
Last NameTham
First NameYow Keat
Address75 Commercial Rd, Melbourne, Victoria, 3004, Australia
Emailyowkeat.tham@baker.edu.au
Phone+65385321266
Submit Date2022-05-18
Num Groups4
Total Subjects25
Num Males10
Num Females15
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2023-01-02
Release Version1
Yow Keat Tham Yow Keat Tham
https://dx.doi.org/10.21228/M89D8V
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Sample Preparation:

Sampleprep ID:SP002321
Sampleprep Summary:tissues was homogenised in 1xPBS and then sonicated with a probe-sonicator for 15 seconds, 23 amplitude. BCA assays were then conducted to determine protein concentrations of these homogenates. Lipid extraction was conducted using 10ul of sample (ventricle, skeletal muscle homogenate at 5mg/ml, fat homogenate at 2mg/ml and liver homogenate at 2.5mg/ml) using the single phase chloroform methanol method. 10ul of internal standards and 200ul of chloroform:methanol (1:2) were added to samples before the mixture was vortexed. Samples were then placed on a rotary shaker for 10 mins at a speed of 90 before being transferred to a bath sonicator. Samples were then sonicated for 30 mins at water temperature below 28 degrees. Samples were then removed and rested at room temperature for 20 mins. Samples were then centrifuged at 13000rpm for 10 minutes. 200ul of the supernatant was then transferred to 0.5ml polypropylene 96 well plates, and spun dried using a speedvac vacuum concentrator. Lipids were reconstituted in 50ul water saturated butanol + 50ul of Ammonium Formate.
Sampleprep Protocol Filename:Agilent_appnote
Extract Storage:-80℃
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